In recent years, with increased awareness of problems of health, environment and safety, a technique for detecting a trace biological or chemical substance involved in these problems has been desired.
However, such a substance to be detected (hereinafter may be referred to as “target substance”) is often included only in a slight amount in a complicated mixture of various substances, and a specimen comprising such a target substance can be collected only in a limited amount. Therefore, detection and measurement of a target substance require high sensitivity, accuracy and reproducibility.
Further, the specimen is often a specimen derived from an organism (hereinafter referred to as “sample”), and it is difficult to acquire the sample. Thus, detection requiring a smaller amount of the specimen has been demanded. This demand for a smaller amount of the sample is also based on the fact that the sample may be a source of infection after disposal, because it is a specimen derived from an organism.
In terms of applications of human clinical laboratory equipment, reduction in the length of time between the acquisition of a sample and the output of detection results, so-called “turn around time”, has been strongly demanded.
As a technique for responding to these demands, a method of improving the reaction efficiency by using a microstructure having a reaction space for trapping a target substance, which is microscopic and has a large surface area per unit volume, has been developed.
Japanese Patent Application Laid-Open No. H03-223674 discloses a reaction vessel for measuring a trace substance in vivo in a simple manner, wherein the reagent fixed parts and/or reagent attached parts formed in a passage through which a fluid flows are concaves and/or small projection aggregates.
Japanese Patent Application Laid-Open No. H09-196920 discloses a body fluid component analyzing instrument having a specimen receiving port, a pump connection port, a specimen treatment region with a specimen labeled with a labeling substance located therein, and a specimen treating and photometric region with a porous material, in which one of a pair of specific bonds is fixed, located therein.
National Publication of International Patent Application No. 2003-514221 discloses a microfluidic device comprising a microchannel for transportation of fluids, wherein the microchannel contains spatially separated defined regions of a specific binding pair member fixed on a porous polymer, beads or microstructures fabricated in the microchannel.
On the other hand, detection methods differing from conventional ones have been now proposed in order to satisfy the above-described demands. Specifically, the detection methods are, as illustrated below, utilize metal-containing microparticles. Metal element-containing microparticles, which have optical characteristics highly sensitive to a slight change in the medium adjacent to the surface of the microparticles, can sensitively recognize a physicochemical change due to the presence of a labeled trace substance.
Japanese Patent Application Laid-Open No. 2000-356587 discloses a localized plasmon resonance sensor which has a sensor unit constituted to have a given substrate and metal microparticles fixed on the surface of the substrate and detects the refractive index of a medium near the metal microparticles by measuring the absorbance of light transmitted through the metal microparticles when the sensor unit is irradiated with light.
Japanese Patent Application Laid-Open No. 2002-365210 discloses a method for detecting living body molecules, characterized in that an apparatus for optically detecting molecular adsorption utilizing optical characteristics of an optical multilayer film, constituted by a substrate, a noble metal thin layer, dielectric microparticles and noble metal microparticles, detects molecular absorption in which, when the optical multilayer film absorbs molecules, the maximum absorption wavelength of the reflection spectrum of the optical multilayer film shifts, but, when the refractive index of a liquid in which the optical multilayer film is immersed changes, the maximum absorption wavelength of the reflection spectrum changes at a level of 1,000 nm or less per unit of the refractive index.
Japanese Patent Application Laid-Open No. 2003-268592 discloses a structure, characterized in that the structure comprises anodized alumina layers, having a plurality of independent pores formed almost perpendicular to the surface of the layers, integrally with mutually isolated metal particles formed with which the respective independent pores are filled, and a sensor, characterized in that the sensor detects the refractive index of a medium near the metal particles fixed on the substrate by measuring the absorbance of light reflected from or transmitted into the metal particles in the structure upon irradiation of the structure with light.
In such a way, various detection chips and devices have now been developed in order to detect a trace target substance. However, it is obvious that a more slight amount of a component must be detected in a short period of time from a small amount of a sample. In addition, it is desirable that clinical laboratory equipment can sensitively detect a trace component as described above and quantitatively measure a component at a high concentration without dilution of a sample.